This invention relates to chiral phospholanes derived from natural products, and asymmetric catalysis using these phospholanes.
Many chiral phosphine ligands have been explored for practical application in asymmetric catalysis, but few chiral ligands or motifs are efficient for the synthesis of commercially useful chiral molecules in industry.
Among known chiral phosphines, several are made from electron-donating chiral phospholanes. One example is the Brunner phospholane shown below. Brunner, H., Organometal. Chem. (1987) 328, 71. However, poor enantioselectivities were observed. 
The ligands DuPhos(trademark) and BPE have been used effectively for certain asymmetric hydrogenation reactions. See U.S. Pat. Nos. 5,329,015; 5,202,493; and 5,329,015; Burk, M. J., J. Am. Chem. Soc. (1991) 113, 8518; Burk, M. J., J. Am. Chem. Soc. (1993) 115, 10125; Burk, M. J., J. Am. Chem. Soc. (1996) 118, 5142. These ligands, however, are not effective for some other asymmetric reactions. Moreover, synthesis of these ligands can be difficult, involving a tedious Kolbe reaction. Also, several liquid DuPhos(trademark)/BPE ligands are air-sensitive and therefore difficult to handle. 
The chiral phosphine RoPhos and its use in Rh-catalyzed asymmetric hydrogenation have been reported. Holz, J. et al., A. J. Org. Chem. (1998) 63, 8031; EP 0889 048. Chiral phosphine X1 has also been reported. Carmichael, D. et al., Chem. Commun. (1999) 261. However, the synthesis is tedious, involving a P stereogenic center.
The inventor has found that it was not possible to make hydroxy analogs of RoPhos using the experimental procedure disclosed in J. Org. Chem. (1998) 63, 8031. A new synthetic route has been developed. Unique properties are associated with hydroxyl phospholanes. An efficient route to these compounds has also been developed by this inventor. Based on this hydroxyl phospholane framework, a polymer chain or a soluble species such as SO3xe2x88x92, PO32xe2x88x92, (CH2CH2O)nCH2CH2OH (n=1, 2, 3) can be introduced.
One aspect of the invention is a ligand of formula A, Axe2x80x2, B, Bxe2x80x2, C, Cxe2x80x2, D, or Dxe2x80x2, or the corresponding enantiomer: 
Another aspect of the invention is a compound of the formula E: 
Another aspect of the invention is a catalyst including one of the compounds A-E above, wherein the compound is in the form of a complex with a transition metal.
Another aspect of the invention is a process for preparing a compound of formula B, by reacting a compound of formula Bx with a phosphine: 
Another aspect of the invention is a process that includes subjecting a substrate to an asymmetric reaction in the presence of one of the above-described ligands, wherein said asymmetric reaction is a hydrogenation, hydride transfer, hydrosilylation, hydroboration, hydrovinylation, olefin metathesis, hydroformylation, hydrocarboxylation, allylic alkylation, cyclopropanation, Diels-Alder, Aldol, Heck, [m+n] cycloaddition, or Michael addition reaction.
Accordingly, one advantage of the invention is in providing chiral ligands that can be made in large scale from inexpensive natural products such as D-mannitol or tartaric acids. Another advantage is in providing new chiral ligands Axe2x80x2-Dxe2x80x2 in FIG. 3, in which the relative configuration of the four stereogenic centers around the phospholane differs from A-D.
Yet another advantage is in providing chiral ligands that are solid and/or more air-stable due to added functional groups, and are more easily handled compared to air-sensitive liquids such as DuPhos(trademark)/BPE ligands. Yet another advantage is in providing chiral ligands that have functional groups on the phospholanes that can be key stereochemistry-defining groups, such as a hemilabile anchor, a hydrogen bonding source, or a cation binding site through a crown ether. Yet another advantage is in providing chiral ligands that have additional functional groups on the phospholanes with water-soluble properties and a convenient site to link a polymer support.
Yet another advantage of the invention is in providing catalysts for a variety of asymmetric reactions such as hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, olefin metathesis, hydroformylation, hydrocarboxylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Aldol reaction, Heck reaction, Baylis-Hillman reaction and Michael addition can be explored based on these innovative ligand systems.
Yet another advantage of the invention is in providing a variety of methods to make both enantiomers of chiral phosphines. Besides D-mannitol, other chiral pool materials such as D and L-tartaric acids can also be used as suitable starting materials for ligand synthesis. Only one phospholane enantiomer can be conveniently obtained using D-mannitol as the starting material while both phospholane enantiomers can be easily obtained when using D and L-tartaric acids for the ligand synthesis.
Both the foregoing general description and the following detailed description of the invention are exemplary and explanatory only and are not necessarily restrictive of the claimed invention.